Epigallocatechin-3-Gallate Therapeutic Potential in Cancer: Mechanism of Action and Clinical Implications

Molecules, Journal Year: 2023, Volume and Issue: 28(13), P. 5246 - 5246

Published: July 6, 2023

Cellular signaling pathways involved in the maintenance of equilibrium between cell proliferation and apoptosis have emerged as rational targets that can be exploited prevention treatment cancer. Epigallocatechin-3-gallate (EGCG) is most abundant phenolic compound found green tea. It has been shown to regulate multiple crucial cellular pathways, including those mediated by EGFR, JAK-STAT, MAPKs, NF-κB, PI3K-AKT-mTOR, others. Deregulation abovementioned pathophysiology demonstrated EGCG may exert anti-proliferative, anti-inflammatory, apoptosis-inducing effects or induce epigenetic changes. Furthermore, preclinical clinical studies suggest used numerous disorders, This review aims summarize existing knowledge regarding biological properties EGCG, especially context cancer prophylaxis.

Language: Английский

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The role and regulation of integrins in cell migration and invasion

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 30, 2024

Language: Английский

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Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 13, 2025

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.

Language: Английский

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Role of Neutrophil Extracellular Traps in Health and Disease Pathophysiology: Recent Insights and Advances

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(21), P. 15805 - 15805

Published: Oct. 31, 2023

Neutrophils are the principal trouper of innate immune system. Activated neutrophils undergo a noble cell death termed NETosis and release mesh-like structure called neutrophil extracellular traps (NETs) as part their defensive strategy against microbial pathogen attack. This web-like architecture includes DNA backbone embedded with antimicrobial proteins like myeloperoxidase (MPO), elastase (NE), histones deploys in entrapment clearance encountered pathogens. Thus NETs play an inevitable beneficial role host's protection. However, recent accumulated evidence shows that dysregulated enhanced NET formation has various pathological aspects including promotion sepsis, pulmonary, cardiovascular, hepatic, nephrological, thrombotic, autoimmune, pregnancy, cancer diseases, list is increasing gradually. In this review, we summarize NET-mediated pathophysiology different diseases focus on some updated potential therapeutic approaches NETs.

Language: Английский

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Cytokines and soluble mediators as architects of tumor microenvironment reprogramming in cancer therapy

Cytokine & Growth Factor Reviews, Journal Year: 2024, Volume and Issue: 76, P. 12 - 21

Published: Feb. 28, 2024

Language: Английский

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Targets of tumor microenvironment for potential drug development

MedComm – Oncology, Journal Year: 2024, Volume and Issue: 3(1)

Published: March 1, 2024

Abstract The tumor microenvironment (TME) is the ecosystem surrounding a tumor, which usually consists of nontumoral cells or components, and molecules they produce release. frequent continuous interplay between TME strongly affects development, disease progression, metastasis, responses to therapeutic interventions. As hub potential targets, has gained appreciable momentum in cancer research. Here we systematically review progress targeting as strategy develop novel antitumor drugs from immunological, stromal extracellular matrix components TME, shedding light on its complex synergies with cells. This exploration highlights transformative these elements hold refining treatment approaches. thorough examination not only accentuates TME's multifaceted nature but also positions it formidable avenue for propelling forward paradigms therapy. aims foster deeper understanding role oncogenesis exploitation advancing targeted, efficacious treatments, marking significant stride realm

Language: Английский

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Understanding the matrix: collagen modifications in tumors and their implications for immunotherapy

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: April 24, 2024

Abstract Tumors are highly complex and heterogenous ecosystems where malignant cells interact with healthy the surrounding extracellular matrix (ECM). Solid tumors contain large ECM deposits that can constitute up to 60% of tumor mass. This supports survival growth cancerous plays a critical role in response immune therapy. There is untapped potential targeting cell-ECM interactions improve existing therapy explore novel therapeutic strategies. The most abundant proteins collagen family. 28 different subtypes undergo several post-translational modifications (PTMs), which alter both their structure functionality. Here, we review current knowledge on composition consequences PTMs affecting receptor binding, cell migration stiffness. Furthermore, discuss how these alterations impact responses could be targeted treat cancer.

Language: Английский

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Targeting the “tumor microenvironment”: RNA-binding proteins in the spotlight in colorectal cancer therapy

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 131, P. 111876 - 111876

Published: March 16, 2024

Language: Английский

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MMP28 recruits M2-type tumor-associated macrophages through MAPK/JNK signaling pathway-dependent cytokine secretion to promote the malignant progression of pancreatic cancer

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Feb. 19, 2025

Abstract Background Crosstalk between pancreatic cancer cells and tumor-associated macrophages (TAMs) is a critical driver of malignant progression, plays an important role in the low response rate to immunotherapy patients with for cancer. Although it known that induce TAM infiltration M2 polarization, underlying mechanisms remain elusive. Herein, we identified matrix metalloproteinase 28 (MMP28), highly expressed protein, as key regulator this process. Methods Immunohistochemical staining qRT-PCR were used validate MMP28 potential marker prognosis We evaluated tumor-promoting effect vitro CCK-8, Transwell, EdU assay Western blotting explored mechanism MMP28-induced polarization TAMs coculture system, immunofluorescence flow cytometry. A subcutaneous graft tumor model was constructed assess its ability infiltration. Results The relevant results study revealed strong correlation expression infiltration, predominance M2-polarized tissues. Mechanistic investigations demonstrated promotes secretion multiple cytokines, including IL-8 VEGFA through activation MAPK/JNK signaling pathway. These cytokines act potent chemoattractants polarizing factors TAMs. Additionally, discovered interaction ANXA2, which contributes regulation recruitment polarization. In vivo studies confirmed growth Depletion macrophages, inhibition JNK, or neutralization significantly suppressed progression. Transcriptomic analysis suggested by modulating amino acid metabolism. Conclusions Collectively, our findings elucidate novel manipulate microenvironment MMP28-dependent cytokine secretion, promoting highlight promising therapeutic target Graphical Schematic overview migration High levels promote mediating phosphorylation signalling pathway then recruiting subsequently metabolism alterations binding receptors on TAMs, ultimately phenotype. addition, ANXA2 increases MMP28-mediated interacting MMP28.

Language: Английский

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Non-Canonical Amino Acids in Analyses of Protease Structure and Function

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(18), P. 14035 - 14035

Published: Sept. 13, 2023

All known organisms encode 20 canonical amino acids by base triplets in the genetic code. The cellular translational machinery produces proteins consisting mainly of these acids. Several hundred natural serve important functions metabolism, as scaffold molecules, and signal transduction. New side chains are generated post-translational modifications, while others have altered backbones, such β- or γ-amino acids, they undergo stereochemical inversion, e.g., case D-amino In addition, number non-canonical has further increased chemical syntheses. Since many confer resistance to proteolytic degradation, potential protease inhibitors tools for specificity profiling studies substrate optimization enzyme inhibition. Other applications include vitro vivo kinetics, molecular interactions bioimaging, name a few. Amino with bio-orthogonal labels particularly attractive, enabling various cross-link click reactions structure-functional studies. Here, we cover latest developments research which opens up great potential, novel prodrugs activated proteases other pharmaceutical compounds, some already reached clinical trial stage.

Language: Английский

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